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Telomeres and Breast Cancer
Welcome! Hi and welcome to our first wiki page! We decided that we wanted to understand more about what role telomeres play in the development of breast cancer. This page will give you general knowledge of telomeres, explain what effects telomerase has on the cells in the body, and provide an understanding of the current cancer treatments and the Cancer Genome Project. Learning Objectives *What are telomeres? *The role of telomerase in breast cancer *What is known about telomere dysfunctions and chromosomal instability *Current treatments and new advances in cancer therapy *The progress of the Cancer Genome Project Telomeres In 1938, a geneticist named Herman Muller discovered that chromosomes have telomeres, which are composed of short DNA sequences, and that they protect the ends of chromosomes from any damage and make sure that the information needed to divide into other cells is not lost. These telomeres are made of thousands of repeats of the TTAGGG nucleotide sequence. In 1940, Barbara McClintock, also a geneticist, found that without telomeres, chromosomes would fuse together, ending the life of the chromosome. Then, in 1961, Leonard Hayflick discovered the "aging clock". He found that there is a limit to the number of times a cell can divide before it dies, known as the "Hayflick limit", and that every time a cell replicates, the telomeres get slightly shorter. When the telomeres get too short, they are near senescence or cell death, and they cannot product healthy daughter cells. At this point, the telomeres can override death by becoming a cancer cell and activating the telomerase enzyme. On Christmas day, in 1984, Elizabeth Blackburn and her graduate student, Carol Greider, found a way to prove that their theory that an enzyme added telomeric DNA to the ends of chromosomes was true. This enzyme, later named telomerase, earned Elizabeth Blackburn, Carol Greider and Jack Szostak the Nobel Prize in Medicine in 1990. The Role of Telomerase in Breast Cancer Telomerase is an enzyme that is not active in most cells, except for germ cells, but has been reactivated to work in cancer cells. The function of telomerase is to lengthen the telomeres by adding more TTAGGG nucleotide sequences to the ends of them. Because the telomeres are continuously getting longer, they become immortal and don't die as they should. This telomore immortality is what gives cancer its strength. As long as there is one cell that still has telomerase activated, the cancer will continue to survive in the body. Telomerase is one of the only things that remains constant between almost every type of cancer. Current Treatments and New Advances in Cancer Therapy There are many types of treatments for breast cancer that include clinical trial and standard. Clinical trial treatment is when patients choose to be a part of work that is being done for further better treatments. Standard studies are treatments that are used on patients currently. The improvement of anodyne, anesthesia, blood transfusion, and cellular biology decreased the number of people diagnosed, through radical surgery. Other treatments such as chemotherapy, energy, surgery and mammography, endocrine therapy and hormone therapy also helped biologist and doctors cure breast cancer. The two most common {C}forms of breast cancer are ductal carcinoma and lobular carcinoma. Ductal carcinoma starts in cells and lines the breast’s ducts that are located beneath the nipple and areola. Lobular Carcinoma is also known to be a duct, but it's deeper inside the breast and it begins in the lobes or the glands of where milk is made in the breast. Gene testing is also used to recognize patients who could be at risk genetically for breast cancer and many other epithelial tumors. Telomere or telomerase therapies may be the upcoming ideal aim for treating cancer worldwide. The extension in length of telomerase gives them a longer time span where they are capable of resisting the threat of cancer cells and are able to reproduce. Telomere Dysfunction and Chromosomal Instability Telomere dysfunction is when the telomeres at the ends of each chromosome don't work as they should. For example, the telomeres may be shorter than they should be, which causes them to look like double-strand breaks (DSBs). Because of this, the chromosomes could fuse together causing chromosome instability. When two chromosomes fuse together, it causes a breakage-fusion-bridge cycle where the chromosomes form a bridge and then break again as the cell attempts to divide itself. Then, the process repeats all over again until the chromosomes gets a new telomere, usually by translocation from another chromosome end. If two sister chromatids fuse together, it results in large inverted repeats at the end of the chromosome and cause more breakage-fusion-bridge cycles. Telomere loss and dysfunction and chromosome instability contribute greatly to human cancer. Telomeres that are uncharacteristically short are often the genetic alterations that cause breast tumors. As an example, in 2009, a case study was conducted to compare the effects of the telomere length of chromosome 9 short arms and long arms with the risk of breast cancer. The results showed that the telomere length of chromosome 9 short arms was much shorter in people with breast cancer than in the control patients. This means that women who have short chromosome 9 short arm telomeres have a greater risk of getting breast cancer and that the two are strongly associated. The Progress of the Cancer Genome Project The Cancer Genome Atlas Project, also called the TCGA Project, is mapping the genetic changes in 20 different cancers, including breast lobular carcinoma and breast ductal carcinoma. Because of these findings involving breast cancer and the BRCA1 and BRCA2 gene mutations, researchers have discovered that women with these mutations that have ovarian cancer are more likely to survive the five year period following the diagnosis than are women that do not have the BRCA1 and BRCA2 gene mutations. There are at least 200 types of cancer and many more subtypes. All cancers are caused by errors in DNA, such as telomere dysfunction, that causes cancer cells to grow uncontrollably. The Cancer Genome Project is working to understand how these changes work together to cause these diseases. The University of California Santa Cruz has opened a 10.3 million dollar cancer genomics club (the CGHub) that will store and make all the data from the major U.S. cancer sequencing projects available. This will make it easier for doctors and researchers to access the information. This project will be working continuously to map all of the cancers. It does not, as of yet, have and end date. Self-Assessment 1. Who discovered telomeres and in what year? a) Herman Muller; 1938 b) Elizabeth Blackburn; 1987 c) Harriet Tubman; 1947 d) Leonard Hayflick; 1961 2. What is the nucleotide sequence of a telomere? a) TCAGTC b) TTAGCG c) ACTATC d) TTAGGG 3. In 2009, a case study was conducted to compare the short and long arms of which chromosome? a) 25 b) 7 c) 9 d) 3 4. Telomerase is an enzyme that isn't active in most cells, except for which? a) germ b) liver c) skin d) colon 5. What happens if two sister chromatids fuse together? a) They disconnect immediately b) breakage-fusion-bridge cycles c) breakage-bridge-fusion cycles d) bridge-fusion-breakage cycles Answers: 1a;2d;3c;4a;5b Annotated Bibliography 1."About TCGA." The Cancer Genome Atlas. Web. 09 May 2012. . *This site was used to help us understand what the Cancer Genome Atlas was and what their goals were. 2. "Breast Cancer Statistics." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 23 Nov. 2010. Web. 6 May 2012. . *This site helped give us statistics of how many women have gotten breast cancer in the United States and how many women died from from having breast cancer. 3. "Breast Cancer Statistics." Susan G. Komen for the Cure. Web. 09 May 2012. . *This site gave us more statistics for people who had breast cancer and compared differenct races and other differences. 4. "Breast Cancer Treatment." National Cancer Institute. National Cancer Institute, 22 Mar. 2012. Web. 5 May 2012. . *This site gave us the treatment options for breast cancer and explained how each one worked. 5. Gilley, David, Brittney-Shea Herbert, and Hiromi Tanaka. "Telomere Dysfunction in Aging and Cancer."ScienceDirect. SciVerse, 14 Nov. 2004. Web. 5 May 2012. . *This articled explains what telomere dysfunction in and what it's role is in cancer. 6. Henderson, Sandy. "The Science Creative Quarterly Â» TARGETING TELOMERES AND CANCER FOR â€˜DUMMIÓ˜Sâ€™." The Science Creative Quarterly Â» TARGETING TELOMERES AND CANCER FOR â€˜DUMMIÓ˜Sâ€™. 2011. Web. 5 May 2012. . *This article helped explain what telomerase is and how it causes cancer. 7. Lu, L., C. Zhang, G. Zhu, M. Irwin, H. Risch, G. Menato, M. Mitidieri, D. Katsaros, and H. Yu. "Telomerase Expression and Telomere Length in Breast Cancer and Their Associations with Adjuvant Treatment and Disease Outcome." National Center for Biotechnology Information. U.S. National Library of Medicine, 6 June 2011. Web. 6 May 2012. . *This articled explained how telomere length effects the chances of getting breast cancer and how that effects the treatments that are available. 8. Murnane, John P. "Telomere Dysfunction and Chromosome Instability." Mendeley Research Networks. Mutation Research, 2011. Web. 7 May 2012. . *This article tells us what a telomere is and gives the definition of telomere dysfunction. It also explains how cancerous cells are formed through telomere dysfunction and chromosomal instability. 9. "The Nobel Prize in Physiology or Medicine 2009." The Nobel Prize in Physiology or Medicine 2009. Web. 6 May 2012. . *This website gave background information about the nobel prize winners and the people who discovered telomeres and telomerase. 10. Zheng, Yun-Ling, Christopher A. Loffredo, Peter G. Shields, and Sahar M. Selim. "Chromosome 9 Arm-specific Telomere Length and Breast Cancer Risk." Oxford Journals: Carcinogenesis. Oxford University Press. Web. 6 May 2012. *This website helped us understand what causes the risk of breast cancer in response to telomere dysfunction and length. It also gave an example of a case study to prove that telomere length does effect cancer risk. Category:Browse